Inflammatory Bowel Disease (IBD) refers to a group of gastrointestinal disorders characterized by a chronic non-specific inflammation of portions of the gastrointestinal tract. Ulcerative colitis and Crohn's Disease are the most prominent examples of IBD in humans. They are associated with many symptoms and complications, including growth retardation in children, rectal prolapse, blood in stools (e.g., melena and/or hematochezia), wasting, iron deficiency, and anemia (e.g. iron deficiency anemia and anemia of chronic disease or of chronic inflammation).
The etiology (or etiologies) and pathogenesis of IBD are still unclear. Previous understanding of the pathogenesis was limited to a three-stage process: (a) an irritant, which could be an immune process or infectious agent, activates (b) leukocytes which release enzymes such as pro-inflammatory cytokines (including tumor necrosis factor alpha (TNF-α), IL-1β and IL-6), proteases and inflammatory mediators such as histamine, serotonin and prostaglandins, and (c) these immunological agents causing edema, pain, heat and loss of function. During the inflammatory process one sees a decline in anti-inflammatory cytokines (including a decline in IL-10). (See, e.g., Wyngaarden and Smith (eds.) Cecil's Textbook of Medicine (W. B. Saunders Co. 1985), Berkow (ed.)), and Harrison's Principles of Internal Medicine, 12th Ed., McGraw-Hill, Inc. (1991)).
Numerous theories implicate multiple factors leading up to IBD including genetic predisposition, environmental factors, infectious agents and immunologic alterations (See e.g., Kirsner, J. B., et al. (eds), Inflammatory Bowel Disease, 3rd ed., Lea and Febiger, Philadelphia (1988); Zipser, R. D., (ed.), Dig. Dis. Sci., 33 Suppl.:1S-87S (1988)). The immunologic alterations in IBD appear to be autoimmune in nature, with autoantibodies and lymphocyte-cytotoxicity directed against intestinal epithelial cells. However, even the latest developments in the immunologic aspects of the pathogenesis of IBD cannot answer the basic question, i.e., whether the detected changes in humoral and cellular immunity reflect a primary defect or secondary response to injury.
Treatment for IBD currently includes steroids, sulphasalazine and its derivatives, and drugs such as cyclosporin A, mercaptopurine and azathioprine. Such therapies are directed toward suppression of the general immune response. These approaches often result in poor success, have little or no selectivity, and can be accompanied by unwanted and sometimes dangerous consequential side effects.